Effects of Endurance Training on Adenosine A2A Receptor Density in Myocardium and Skeletal Muscle

Abstract

0182 Adenosine is an endogenous modulator of several physiological functions in the central nervous system as well as peripheral organs such as myocardium and skeletal muscle. The effects are mediated by at least four subtypes: A1, A2A, A2B, and A3 receptors. In particular, adenosine A2A receptor is involved in myocardial contractility and glucose utilization in the skeletal muscle. PURPOSE: The primary aim of the present study is to evaluate adenosine A2A receptors in the myocardium and skeletal muscle in humans with positron emission tomography (PET) and [7-methyl-11C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([11C]TMSX), a potential radioligand for mapping adenosine A2A receptors. Second goal is to investigate the effects of endurance training on the densities of adenosine A2A receptors in myocardial and skeletal muscle. METHODS: Four untrained (24±2 yrs) and three endurance-trained subjects (triathlete, 22±2 yrs) participated in this study. The values of peak oxygen uptake were measured during both cycling and arm-cranking exercise. The density of adenosine A2A receptors was evaluated as the distribution volume of [11C]TMSX in the left ventricular myocardium and upper limb muscle (triceps brachii) in the resting state with PET. RESULTS: The peak oxygen uptake was significantly higher in the trained subjects than in the untrained subjects (cycling: 68±3 vs. 47±8 mL/kg/min, p<0.05; armcranking: 38±2 vs. 31±4 mL/kg/min, p<0.05). The distribution volume of [11C]TMSX in the myocardium was much larger than that in the upper limb muscle (3.0±0.4 vs. 0.5±0.2 g/mL, p<0.05). The distribution volumes in the myocardium were not different between in the untrained and endurance-trained groups (2.8±0.3 vs. 3.3±0.5 g/mL, respectively, p = 0.15). In contrast, the densities of adenosine A2A receptors in the upper limb muscle were significantly different between the two groups: the distribution volume in the endurance-trained group was significantly higher than that in the untrained group (0.4±0.1 vs. 0.8±0.1 g/mL, p<0.05). CONCLUSION: These results indicate that the density of adenosine A2A receptors in the myocardium was much highly than that in skeletal muscle, and that endurance training may increase the density of adenosine A2A receptors in the skeletal muscle, but not in the myocardium.